This proposal arises out of a long-term effort by the PI to define the molecular mechanisms underlying behavioral plasticity, using songbirds as a model. Previous studies have shown that induction of a specific gene ("ZENK") occurs in specific parts of the songbird forebrain, in response to a normal perceptual experience -- hearing the sound of other birds singing. We have now found that this ZENK gene response is modified by recent experience: if a particular song is repeated for an hour the response to that song fades, but a new conspecific song from a different individual will immediately reinduce it. The aim of this project is to assess the functional significance of this experience- dependent change in gene expression in the brain. To this end, we will determine whether specific electrophysiological responses occur in response to conspecific birdsong in the caudomedial neostriatum ("NCM"), which is the primary site of ZENK gene induction and an avian homolog of mammalian neocortex. Experience-dependent physiological responses will be analyzed by counting the number of spikes elicited during auditory stimulus presentation, using "near-single-unit" recording techniques. In preliminary studies, we have successfully made such measurements in NCM in zebra finches, and have found evidence for a variety of song-selective changes in auditory responses. The specific aims of the proposed study are to: l) characterize the selectivity of auditory responses in NCM and related brain regions; 2) determine whether ZENK induction is anatomically correlated with sites of physiological plasticity; 3) determine whether production of ZENK protein is temporally correlated with consolidation of physiological change; 4) evaluate whether ZENK induction may have a role in song learning in juveniles; 5) evaluate whether ZENK induction is correlated with other specific behavioral changes in adults. A role for gene expression in guiding the brain's response to experience has long been hypothesized, and the songbird has unique advantages as a model system for testing this hypothesis. These advantages include a controlled perceptual stimulus (song), a defined neural circuit within parts of the brain homologous to the mammalian neocortex, and now the identification of specific gene responses within this circuitry. Clarification of the role gene expression plays in the brain's response to experience could have a major impact on our ability to analyze and treat numerous psychiatric, neurodegenerative and learning disorders.